30/06/2016

A 62-year-old pharmaceutical drug developed by the Burroughs Wellcome Co. hit the news recently when the drug company who purchased the US marketing rights and increased the price by 5,000%.

Today pyrimethamine (brand name Daraprim) is mainly used to treat toxoplasmosis in those with compromised immune systems such as AIDS and cancer patients. It has a place on the World Health Organization’s List of Essential Medicines as an anti-infective drug. But it was originally developed as an anti-malarial.

Daraprim was the result of a close collaboration between the Wellcome Research Laboratories at Tukahoe in the USA and the Wellcome Laboratories of Tropical Medicine in London (now the home of Wellcome Collection) in the 1950s.

It was just one of many drugs developed by Gertrude Elion, who was Head of the Department of Experimental Therapy at Tukahoe from 1967-1983. She and long term collaborator George Hitchings used ‘rational drug design‘ to produced a number of other “blockbuster” drugs such as Imuran, Septrin, Zovirax and AZT. Elion’s portrait now hangs in the Elion & Hitchings room at the Wellcome Trust.

Following Elion’s laboratory work in the US, the drug was ‘field’ tested by the UK team under Dr Len Goodwin. As he later explained:

“it was quite a different kind of clinical trial from the kind done today, because there were no lawyers looking over our shoulders with regulations, and it didn’t cost you £100 million in order to get the drug passed by the US Food and Drug Administration (FDA). So when we’d got something that worked reasonably well on laboratory infections, we took a few doses ourselves to determine the basic pharmacodynamics and then persuaded somebody to let us try it in the field. I don’t really think we did very much damage, and I think we did a bit of good.” (Witness Seminar, 2001, p90)

Advert for Daraprim in the Chemist and Druggist, 2 June 1956.

To say they took “a few doses” themselves was an understatement. His colleagues reported that “Len gave himself large doses for a year and, while on a trip in Africa, he had no other protection from malaria. While passing through Kenya, he allowed mosquitoes infected with the deadliest malaria parasite, Plasmodium falciparum, to feed on his arm.”

Len Goodwin, from an article about him in the Chemist and Druggist, 4 October 1958.

And during the development of pyrimethamine, he took a dose that rose to 100mg a day but this had to be stopped as the production of red blood cells in his bone marrow was adversely affected. As a result of these studies, the recommended and effective dose of the drug was established as 25mg, once a week. Fortunately the trials proved successful and the Burroughs Wellcome Co. threw the weight of its marketing machine behind the drug.

Burroughs-Wellcome & Co. merged with Glaxo to become Glaxo Wellcome in 1995, eventually dropping the Wellcome, and after subsequent mergers becoming GlaxoSmithKline. In 2010, GlaxoSmithKline sold the marketing rights for Daraprim. The US rights were eventually acquired, in August 2015, by Turing Pharmaceuticals, although it is also produced around the world, in its unbranded form, as pyrimethamine.